Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease.

摘要: In humans, complex I of the respiratory chain is composed seven mitochondrial DNA (mtDNA)-encoded and 38 nuclear-encoded subunits that assemble together in a process poorly defined. To date, only two assembly factors have been identified how each functions not clear. Here, we show human factor CIA30 (complex intermediate associated protein) associates with newly translated mtDNA-encoded at early stages their before dissociating later stage. Using antibodies CIA30-deficient patient who presented cardioencephalomyopathy reduced levels activity I. Genetic analysis revealed had mutations both alleles NDUFAF1 gene encodes CIA30. Complex cells was defective being degraded. Complementing deficiency fibroblasts normal using novel lentiviral system restored steady-state levels. Our results indicate crucial component its can cause disease.